Inflammation and Cardiovascular Disease

Abstract

Inflammation plays an important role in the development and progression of a variety of cardiovascular conditions, most notably coronary atherosclerosis and congestive heart failure.1,2 A number of inflammatory molecules have been implicated in these processes, including interleukin-1 (IL-1). The IL-1 gene family consists of 3 proteins, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra). IL-1α and IL-1β exert their similar effects by binding to the IL-1 type I receptor. The IL-1 type II receptor also binds IL-1α and IL-1β but acts as a decoy receptor and is not involved in signal transduction, thereby counterbalancing the inflammatory effects of IL-1α and IL-1β. IL-1ra is an endogenous inhibitor of IL-1α and IL-1β, which competitively binds to the IL-1 type I receptor without activating it.3 Article p 2662 Both IL-1 and IL-1ra are produced by endothelial cells, smooth muscle cells, and macrophages. IL-1 secretion is induced by microbial products that stimulate toll-like receptors and by certain endogenous triggers, such as uric acid produced during cell death. Both types of agonists stimulate a cytosolic complex of proteins termed the inflammasome, which activates caspase-1 to enable secretion of IL-1β. The potential of this IL-1β pathway for systemic inflammation is demonstrated not only by gout but also by the clinical effects of activating mutations in cryopyrin (also known as NALP3 or CIAS1), one of the inflammasome components, which causes familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease.4 Circulating levels of IL-1 are associated with the presence of traditional cardiac risk factors, such as diabetes mellitus, hypertension, smoking, and dyslipidemia. Elevated levels of IL-1 result in secretion of chemokines and other cytokines (eg, IL-6), increased expression of adhesion molecules, activation of endothelial and smooth muscle cell proliferation, macrophage activation, and increased vascular permeability. This cascade promotes atherosclerosis and plaque destabilization. IL-1 and …